Principal Component Analysis Provides Insights on the Evolutionary Divergence of Conotoxins

Conotoxins are fast-evolving and highly diverse small, structured peptides found in venoms of predatory marine gastropods of the genus Conus. They are diverse yet exhibit superior stability, potency, and selectivity for various target receptors and subtypes; hence, they were proven valuable probes for drug discovery studies and models for protein evolution. The data structure of conotoxin peptide sequences in each gene superfamily was analyzed. Feature extraction showed diet- and geographical region-specific gene superfamilies. Using fast-Fourier transform (FFT) and principal component analysis (PCA), data structures indicated patterns of sequence similarity in conopeptides isolated in the same diet type. Clusters based on diet are prominent in the PCA plots and dendrograms. PCA clustering, node grouping, and feature extraction suggest the increasing role of dietary preference, providing insights on the driving force that pushed conotoxins to diverge and diversify.